rs138590000

Variant names:

• chr18-34877815-T-C
• rs138590000
• NM_001386795.1:c.1993+7T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-34877815-T-C
• chr18-34877815-T-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001386795.1(DTNA):​c.1993+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000708 in 1,612,612 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: DTNA NM_001386795.1 splice_region, intron
• Scores: Splicing: ADA: 0.00003073
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.299
• Publications: 0 publications found

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNA Gene-Disease associations (from GenCC):

• left ventricular noncompaction 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Meniere disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-34877815-T-C is Benign according to our data. Variant chr18-34877815-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 564 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	NM_001386795.1	MANE Select	c.1993+7T>C		splice_region intron	N/A	NP_001373724.1	A0A7P0TBH9
	DTNA	NM_001386788.1		c.1993+7T>C		splice_region intron	N/A	NP_001373717.1	Q9Y4J8-17
	DTNA	NM_001390.5		c.1912+7T>C		splice_region intron	N/A	NP_001381.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	ENST00000444659.6	TSL:5 MANE Select	c.1993+7T>C		splice_region intron	N/A	ENSP00000405819.2	Q9Y4J8-17
	DTNA	ENST00000598334.5	TSL:1	c.1732+7T>C		splice_region intron	N/A	ENSP00000470152.1	Q9Y4J8-15
	DTNA	ENST00000399121.9	TSL:1	c.1753+7T>C		splice_region intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152208 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00100 AC: 252 AN: 251260 AF XY: 0.000817

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000395 AC: 577 AN: 1460286 Hom.: 4 Cov.: 30 AF XY: 0.000323 AC XY: 235 AN XY: 726554

African (AFR) AF: 0.0137 AC: 460 AN: 33460

American (AMR) AF: 0.000514 AC: 23 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1110684

Other (OTH) AF: 0.00109 AC: 66 AN: 60318

GnomAD4 genome AF: 0.00370 AC: 564 AN: 152326 Hom.: 7 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74500

African (AFR) AF: 0.0130 AC: 541 AN: 41584

American (AMR) AF: 0.000980 AC: 15 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00122 Hom.: 1

Bravo AF: 0.00419

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Left ventricular noncompaction 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138590000; hg19: chr18-32457779;